Technical Field
The present invention relates to a process for the preparation of ospemifene and pharmaceutically acceptable salts thereof which comprises the step of recycling the undesired E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol to generate an isomeric mixture of Z,E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol.
Description of the Related Art
Ospemifene, also known as Z-2-[4-(4-chloro-1,2-diphenylbut-1-enyl)phenoxy]ethanol, is represented by the structure of formula I.

Ospemifene is an estrogen agonist/antagonist indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Ospemifene is marketed under the brand name OSPHENA® in the United States.
There is no teaching in the art for the preparation of ospemifene wherein the undesired intermediate E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol formed as a by-product, is recycled for increasing the productivity of the desired Z-isomer which is used for preparing ospemifene.
There is a need in the art, therefore, for a cost-effective synthesis of ospemifene, which would be advantageous over the reported processes known in the art.
The object of the present invention is to provide a process for the preparation of ospemifene comprising recycling the undesired E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol to generate an isomeric mixture of Z,E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol, isomeric separation of the desired Z-isomer from the Z,E-mixture, optionally repeating the recycling and isomeric separation steps and converting the desired Z-isomer to ospemifene.